The purpose of this project is to define the mechanism of regulation of the individual globin genes during erythroid differentiation. Total genomic DNA from sheep, homozygous for the BA globin gene, has been cut into fragments of 10-20 kb in length by restriction endonuclease digestion and cloned into E. coli using the vector, bacteriophage Charon 4A. Individual recombinants containing globin gene sequences have been identified. The BA, gamma, and epsilon globin genes have been characterized; each contains a large and small sequence. The presence of a restriction endonuclease site for Pvu II at the 5' end of the gene suggests sequence homology in this region. Further analysis of these isolated globin genes is planned in an attempt to determine the role of DNA sequence in regulating hemoglobin switching.